The principal objective of this project is to apply state-of-the-art gas chromatographic/mass spectrometric methodologies to the analysis of trace levels of fatty acid metabolites in an effort to elucidate the molecular alterations involved in various neuropathological states. These compounds are generally potent agents that are present in extremely low levels or in such complex mixtures that other techniques often cannot provide reliable results. During the first phase of this research, emphasis has been placed on characterizing the levels of prostaglandins in human cerebrospinal fluid (CSF). Preliminary investigations have suggested that prostaglandin levels in CSF drawn from patients with neurological impairment are markedly altered from those of normal volunteers. The levels are often near or below the reported detection limits of 10-100 pg/mL of CSF. The results described in this study summarize the methodologies used to demonstrate significantly lower levels of detection for application to the analysis of CSF samples from a variety of patient groups. Of particular importance is the application of these methodologies for the first time to samples of CSF drawn from alcoholic patients during withdrawal.